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| Status |
Public on Sep 03, 2020 |
| Title |
Kevetrin induces apoptosis in TP53 wild-type and mutant acute myeloid leukemia cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Tumor protein p53 is a key regulator of several cellular pathways, including DNA repair, cell cycle and angiogenesis. Kevetrin exhibits p53-dependent as well as independent activity in solid tumors, while its effects on leukemic cells remain unknown. We analyzed the response of acute myeloid leukemia (AML) cell lines (TP53 wild-type: OCI-AML3 and MOLM-13; and TP53-mutant: KASUMI-1 and NOMO-1) to kevetrin at a concentration range of 85-340 μM. Kevetrin induced cell growth arrest and apoptosis in all cell lines and in primary cells, with TP53-mutant models displaying a higher sensitivity and p53 induction. Gene expression profiling revealed a common core transcriptional program altered by drug exposure and the downregulation of glycolysis, DNA repair and unfolded protein response signatures. These findings suggest that kevetrin may be a promising therapeutic option for patients with both wild-type and TP53-mutant AML.
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| Overall design |
MOLM-13 and KASUMI-1 cell lines treated with Kevetrin (or vehicle) for 6h and 48h were used for RNA extraction and hybridization on microarrays.
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| Contributor(s) |
Simonetti G, Napolitano R, De Matteis S, Martinelli G |
| Citation(s) |
32945487 |
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https://0-doi-org.brum.beds.ac.uk/10.3892/or.2020.7730
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| Submission date |
Sep 17, 2019 |
| Last update date |
Oct 02, 2020 |
| Contact name |
Giorgia Simonetti |
| E-mail(s) |
giorgia.simonetti@irst.emr.it
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| Organization name |
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"
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| Lab |
Giorgia Simonetti
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| Street address |
Via Piero Maroncelli, 40
|
| City |
Meldola |
| State/province |
FC |
| ZIP/Postal code |
47014 |
| Country |
Italy |
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| Platforms (1) |
| GPL17586 |
[HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version] |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA565968 |
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